YARGESA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YARGESA (YARGESA).
YARGESA is a monoclonal antibody that binds to and inhibits programmed cell death protein 1 (PD-1), blocking the interaction with its ligands PD-L1 and PD-L2, thereby enhancing T-cell-mediated immune response against cancer cells.
| Metabolism | YARGESA is a monoclonal antibody, expected to be degraded into small peptides and amino acids via general protein catabolic pathways; no specific metabolic enzymes are involved. |
| Excretion | Biliary/fecal: 90%; renal: 10% |
| Half-life | Terminal elimination half-life: 12-15 hours. Clinical context: No dose adjustment needed for mild-moderate renal impairment; caution in severe hepatic impairment. |
| Protein binding | 97% bound primarily to albumin |
| Volume of Distribution | Vd: 0.8-1.0 L/kg, indicating extensive tissue distribution |
| Bioavailability | Oral: 85-90% |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours; Intravenous: 4-6 hours. Clinical notes: Duration may be prolonged in hepatic impairment. |
Leuprolide acetate 22.5 mg subcutaneously every 12 weeks.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for renal impairment; pharmacokinetics not significantly altered. |
| Liver impairment | No dose adjustment required for hepatic impairment; metabolism not hepatic-dependent. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; monitor for hypersensitivity and cardiovascular effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for YARGESA (YARGESA).
| Breastfeeding | It is unknown whether YARGESA is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 3 months after the last dose. No M/P ratio data are available. |
| Teratogenic Risk | YARGESA is contraindicated in pregnancy. Based on its mechanism of action and animal studies, there is a high risk of fetal harm, including structural anomalies and fetal demise, throughout all trimesters. Effective contraception must be used during treatment and for at least 3 months after the last dose. |
■ FDA Black Box Warning
Immune-mediated adverse reactions: YARGESA can cause severe or fatal immune-mediated adverse reactions due to T-cell activation, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, and solid organ transplant rejection.
| Serious Effects |
None
| Precautions | ["Immune-mediated pneumonitis: monitor for cough, chest pain, dyspnea; withhold or permanently discontinue based on severity","Immune-mediated colitis: monitor for diarrhea, abdominal pain; treat with corticosteroids if grade 2 or higher","Immune-mediated hepatitis: monitor liver function; withhold or discontinue based on severity","Immune-mediated endocrinopathies: monitor for hypophysitis, thyroiditis, adrenal insufficiency; manage with hormone replacement","Immune-mediated nephritis: monitor renal function; treat with corticosteroids if grade 2 or higher","Infusion-related reactions: monitor for fever, chills, hypotension; interrupt or slow infusion","Embryo-fetal toxicity: can cause fetal harm; advise effective contraception"] |
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| Fetal Monitoring | Monitor complete blood counts, hepatic function, renal function, and electrolytes at baseline and periodically during therapy. For females of reproductive potential, perform pregnancy testing prior to initiation and monthly during treatment. Monitor for signs of infection, bleeding, and thromboembolic events. |
| Fertility Effects | Based on animal studies, YARGESA may impair male and female fertility. In females, it may cause ovarian failure and reduced fertility. In males, it may cause testicular toxicity and oligospermia. Fertility may not be reversible. |